Current Projects
ProjectsMathematical Modeling of Iron Metabolism
Iron in ionic form is absolutely indispensable for life, but is also a severe poison if accumulated. Iron depletion is one of the most frequent pathological states – iron poisoning a frequent genetic defect. Balance between not enough and too much is extremely difficult and is being maintained mainly by the liver and the Reticulo Endothelial System (RES) as regulator instances.
We are at present developing systems biology of iron in the human body as part of Hepatosys Initiative. This comprises a theory of iron balance and regulation in each in individual cell as well as a global balance and regulation of organs in the whole organism. A first stage has been reached: we present a flux balance model of iron in the whole body. It is mainly based on published isotope studies in numerous clinical settings. Tiny amounts of radioactive iron do not disturb the balance state of the body, but may serve as empirical marker of the fluxes between cells and organs, including uptake in the intestine and desquamation of body cells. This situation can be described by linear differential equation. The resulting flux model displays a pronounced flux and time hierarchy. It is adequate to mimic the main empirical results obtained by iron dose into blood plasma, into the stomach and as damaged red blood cells indirectly into the phagocytic system of RES.
The next step of this project is the molecular level. Since we developed an understanding of the upper “layer” of regulation (the organs), we believe that this will help to characterize the picture of cellular and molecular iron regulation. For this purpose we count on expertise from our co-workers in Heidelberg, Dr. Martina Muckenthaler and Dr. Matthias Hentze, who have been working with iron related topics and mouse models for years.